Abstract: To investigate the inhibitory effects and mechanisms of chicoric acid (CA) on hepatocellular carcinoma (HCC), this study employed an integrated approach combining network pharmacology, molecular docking, and experimental validation to analyze its multi-target mechanism systematically. Swiss Target Prediction database was used to predict the potential target of CA, while Liverome and Onco DB.HCC databases were integrated to screen HCC-related targets. The protein interaction network was constructed using Cytoscape, followed by GO (Gene Ontology) biological function and KEGG (Kyoto Encyclopedia of Genes and Genes) pathway analyses via the DAVID database. Molecular docking between CA and core targets was performed using AutoDock. Finally, in vitro Hepa1-6 cell experiments were conducted to evaluate the inhibitory effect of CA on HCC cell viability and migration by CCK8 assay, cell scratch test, and mRNA analysis of key genes. The key pathways predicted by network pharmacology were verified by western blotting. In this study, 103 potential targets of CA, 1007 targets of HCC, and 31 intersection targets were screened. The core targets involved serine/threonine kinase 1 (AKT1) and phosphatidylinositol 4, 5-diphosphate 3-kinase catalytic subunit α (PIK3CA). GO enrichment analysis highlighted processes such as cytoplasm, protein binding, and protein hydrolysis, while KEGG analysis revealed enrichment in the PI3K-Akt signaling pathway and cancer pathway. Molecular docking results showed that CA had good binding activity with the key targets PI3K and AKT. In vitro cell experiments demonstrated that CA significantly inhibited the proliferation and migration capabilities of HCC cells, downregulated the mRNA expression of tumor growth-related genes Egfr and Mmp2, and reduced the phosphorylation levels of PI3K and AKT protein. While PI3K-Akt pathway agonists induced the proliferation and migration of Hepa1-6 cells, CA effectively suppressed the progression of HCC cells and downregulated the expression of p-PI3K and p-AKT. This study preliminarily revealed that CA inhibited the proliferation and migration of HCC cells by regulating the PI3K-Akt signaling pathway. The integration of network pharmacology, molecular docking, and in vitro experimental validation provides a scientific basis for an in-depth study of the mechanism of action of CA against HCC.